The overall purpose of this competing continuation is to expand our understanding of the processes associated with the development of substance use and high-risk sexual behavior from early childhood through emerging adulthood, and the processes leading to addiction and dependence in emerging adulthood. The original study began with the assessment of 1075 youth, their parents and teachers, when youth were in first through fifth grade, enabling a multi-source assessment of etiological factors measured at a young age. Annual assessments across ten years, with minimal attrition, have provided extensive data on over 950 youth, following them until they are in the 10th grade through one year post high-school. Together with the original study, the proposed data collection will extend the follow-up to one-year post high school for all youth, and add an in-depth assessment of all participants when they reach age 20/21 consisting of a diagnostic interview and a social stress test to assess cortisol reactivity. A developmental/contextual framework examining the interaction of etiological factors across four systems, biological, cognitive, personality and social, guides our research questions addressing five aims: (1) Examine the processes explaining continuity and discontinuity of the development of substance use from early childhood through adolescence and into emerging adulthood; (2) Further the understanding of the relation between the development of substance use and at-risk sexual behavior, identifying unique and common predictors; (3) Further the understanding of the relation between childhood stress and stress in emerging adulthood, and substance use and abuse/dependence and high risk sexual behavior; (4) Further the understanding of the relation of substance use to the assumption of adult roles in emerging adulthood; and (5) Assess the generalizeability of models developed with data from our primarily Caucasian sample by examining the fit of models using data from a sample consisting primarily of African Americans, the Family and Community Health Study (FACHS). Unique novel features of this study include the length of follow-up (first grade to age 21), annual assessments during childhood and adolescence enabling the identification of classes of trajectories, and the integration of psychological with biological variables. The assessment in emerging adulthood of cortisol reactivity, a biological marker of stress associated with substance use and addiction, further expands the etiological framework underpinning this project. The generality and importance of findings from this project will be extended significantly through collaboration with the FACHS by enabling a comparison of etiological processes between African American and primarily Caucasian youth. These findings will guide future prevention and intervention efforts for youth by identifying etiological processes occurring from the early elementary years through emerging adulthood that place individuals at risk or that are protective, including the relation between stress reactivity and addiction.